Осмотски пумпи- системи за контролирано ослободување на лекови

Унапредувањето на постоечката фармакотерапија се одвива кон развој на лекови кога е потребно селективно да делуваат со цел да се редуцира фреквенцијата на дозирање или да се зголеми ефективноста на дрогата со локализација на местото на делување што води до намалување на потребната доза или обезбедување на униформна испорака на лекот. Исто така, употребата на современите фармацевтски дозирани форми е оправдана од аспект на минимизирање и елиминација на несаканите ефекти и зголемување на безбедносната граница со примена на високопотентни активни супстанци. Генерално, конвенционалните дозирани форми се карактеризираат со низа недостатоци: • слаба комплијанса од пациентите, зголемена можност за пропуштање на дозата на лековити супстанци со краток полуживот за кои е неопходна честа администрација. • варијациите во концентрацијата на лековитата супстанца водат до предозирање или субдозирање и отежнато постигнување на рамнотежната состојба Најперспективен начин за надминување на недостатоците карактеристични за конвенционалната фармакотерапија е инкорпорирањето на активните супстанци во соодветни носачи што обезбедува контролирано ослободување и висока биорасположивост. Истражувањата покажуваат дека потребата од дозирање повеќе од еднаш или два пати дневно значително ја намалува комплијансата на пациентот. Од различните системи за испорака на лекови достапни на пазарот системите со контролирано продолжено ослободување за орална употреба имаат најголем потенцијал поради нивните очигледни предности- лесната администрација и зголемената комплијанса од страна на пациентите. Овие системи обезбедуваат значителен бенефит над формулациите со моментално ослободување овозможувајќи поголема ефективност на третманот на хроничните заболувања, намалени несакани ефекти и поголем степен на комфор кај пациентите во однос на поедноставеното дозирање. Системите за контролирано ослободување даваат предвидливост и репродуцибилност во кинетиката на ослободувањето на лекот. Перспективни претставници за обезбедување на контролирано ослободување се осмотските пумпи кои работат на принцип на осмоза и генерално го користат протокот на растворувачот за активација

Correlation of H-bonding distances and strengths in API solvates case study on nitrofurantoin and pyridoxine

Hydrogen bond solvation affects molecular properties and functions both in solution and solid-state formation of solvates. Many of Active Pharmaceutical Ingredients (APIs) exist as solvates with different solvents that, depend on the nature and polarity, co-crystallize with their appropriate molecular structures in wide range of polarity, either non-ionizable or deprotonated acids and bases and their protonated forms, respectively. Despite H-bonding networking that occurs in a highly competitive solvent in biological systems, synthetic chemists have been facing with difficulties to control and predict the H-bonding motifs from de novo in competitive solvents media. The concept of crystal engineering, based on molecular noncovalent recognitions and formation of self-assembled supramolecular clusters opens the opportunities for designing the solvate type of crystals with desirable properties [1]. The crystallographic parameters of the determined crystal structure of two types of API solvates are presented. The N,N dimetileformamide solvate of the chemotherapeutic class of API for treatment of urinary infection, nitrofurantoin and hydrated form of molecular salt that pyridoxine (vit B6) form with ferulic acid (derivate of hydroxybenzoic acid) [2,3]. The correlation of the H-bond distances with the bond strength are depicted on Hirshfeld surface’s 2D fingergerprint plots. Though many of solvents are not with pharmaceutical relevance in terms of their high risk for toxicity, their co-crystallization with API molecules in crystalline systems offer opportunities to analyze the H-bond patterns and study the propensity of occurring the motifs i.e., synthons among solvated crystals that are deposited in Cambridge Crystal Crystallography Database (CCCD). Keywords: Crystal engineering, solvates, Hydrogen bonding, molecular recognition Literature 1. N. Y. Meredith, S. Borsley, I. V. Smolyar, G. S. Nichol, C. M. Baker, K. B. Ling, S. L. Cockroft, Angew. Chem. Int. Ed. 2022, 61, e202206604; Angew. Chem. 2022, 134, 2. Cvetkovski, A., Ferretti, V. Crystal Structure and Packing Analysis of Nitrofurantoin N,N-dimethylformamide Solvate. Crystallography Reports, (2016) 4. 1063-7745 3. Cvetkovski, A., Ferretti, V., Bertolasi, V. New pharmaceutical salts containing pyridoxine. Acta Crystallographica Section C: Structural Chemistry, Acta Cryst. (2017), C (73), 1064-107

Influence of beta-cyclodextrin on the phase transition in carbamazepine polymorphs

Results confirm that phase transition of CBZ polymorphs, anhydrous form III and I leading to less water soluble CBZ pseudopolymoprph, dihydrate form during the kneading and formation of IC with BCD occur simultaneously. Less water soluble and stable at ambient temperature CBZ III, thus less favorable for transition in CBZ dihydrate, in grinded binary sample with BCD exerts higher water solubility due to formation of IC. BCD in high extent retains inhibition of phase transition of CBZ III to CBZ I during the DCS heating cycle. ICs as immediate release drug delivery systems offer further opportunities for design modified release formulations that may include IC in combination with a polymeric matrix formation compound for additional control of both the drug release profile and drug phase transition

Influence of beta-cyclodextrin on the phase transition in carbamazepine polymorphs

Carbamazepin (CBZ), a widespread used antiepileptic drug, branded as Tegretol, firstly was launched in form of Active Pharmaceutical Ingredient (API) as a commercially available polymorphic form III. Additionally, crystallographic studies on crystal packing motifs of carbamazepine molecules in crystal lattices, reveal that, a part of the firstly confirmed structure of polymorphic form III, this drug exists in three other polymorphic forms I, II and IV, as well as pseudopolymorph, dihyrdate form. [1] Further solid-state testing confirmed that in terms of thermodynamical stability CBZ III and I are related as enantiotropic pair, former exerting higher stability at ambient temperatures, up to phase transition temperature (Tt≈71℃) when it is transformed in the later with melting temperature at 193 ℃. Due to the polarity of the CBZ molecule that is carbamylated derivative of iminostilbene, consequently that determine its lipophilicity, CBZ belongs to BCS class II of low water solubility and high permeability drug. Compromising the differences in crystal packing between CBZ polymorphs III and I that exert differences in density and solubility with the requirements for sufficient plasma concentration available for favorable crossing the blood-brain barrier (BBB) and reaching receptor sites, remain the challenge for crystal engineering CBZ polymorphs with functional excipients which, based on their molecular structures, are appropriate for formation either of inclusion complexes (IC) or co-crystals (CC). In terms of processing the CBZ polymorph, either with solvents or by mechanochemical treatments, both technologies impose phase transition; the first one causes transformation of anhydrous polymorphs to CBZ dihydrate, and second lead to interconversion of stable to metastable forms by thermomechanical activation on crystal particle surface [2]. The outlined research objectives address the testing of the influence of beta cyclodextrin (BCD), native cyclic oligosaccharide, on controlling the phase transition of CBZ form III to form I, respectively toward the formation of inclusion complex by non-covalent interactions between nonpolar part of CBZ molecule and hydrophobic CBD cavity that interact each other in stoichiometric ratio

Influence of mechanochemical processing to phase transition of carbamazepine polymorphs and formation of Inclusion Complex with cyclodextrin

Upon grinding both the reactivity and the reaction selectivity are usually improved resulting in a reduced reaction time and a decreased number of purification steps. Role of Mechanochemistry in Inclusion Complexes (ICs) formation The solid-state reactivity is much more linked to diffusion phenomena in the crystalline parts of the material than to the increase in the surface area of the CD particles resulting from grinding. supramolecular effects (diffusion through channels) the reaction rate is not directly proportional to the aggregate total active area of contact between the reactants mechanically assisted reaction proceeds with higher selectivity with change of pH value The quantification of the grinding contribution in the reactivity was lacking at this stage (it was not clear whether the increase in reactivity was only a consequence of the formation of inclusion complexes, or whether the grinding process was also involved). Water molecule in cavity loses out 2 H-bonds, higher degree of freedom; enthalpically driven hydrophobic inclusion Outline of the lecture: Molecular & Crystal Structures of Cyclodextrins (CDs) The Crystal Structure of drug model Carbamazepin (CBZ) polymorphs III & I CD Inclusion Complexes (ICs) Role of Mechanochemistry in IC formation Experimental Design for IC CBZ polymorphs / BCD Result

Evaluation of topical preparations of meloxicam

Aim of the study: Meloxicam is a non-steroidal, anti-inflammatory medicine that exhibits highly potent analgesic, antipyretic activity indicated for pain in patients with rheumatoid arthritis, osteoarthritis etc. Despite the fact that this medicine possesses some COX-2 selectivity over COX-1, it is not considered as COX-2 inhibitor by FDA. Compared with other NSAID, meloxicam is relatively safer, but unfortunately is associated with gastrointestinal adverse effects. Currently commercial forms of meloxicam are tablets, oral suspension and injections. An intriguing strategy to overcome these limitations is formulation of topical dosage forms for transdermal delivery. Present study reports a detail review of data from clinical studies of different formulations of topical meloxicam, methods of preparation and characterization of their structure, the influence of various parameters on the stability and the market’s patented formulations by now

Parenteral preparations

The lecture is focused on principles of parenteral formulation, sterility testing, storage and packaging

Analysis of consumption of insulin in the municipality of Stip from 2011 to 2014

Diabetes mellitus is a syndrome characterized by chronic hyperglycemia and disorder of the metabolism of carbohydrates, protein and fat associated with a relative or absolute lack of insulin secretion and insulin action. Diabetes is one of the most common endocrine disorders, with a tendency of increased growth. It is a consequence of modern lifestyles and the increasing number of internal, genetically conditioned and external etiological triggers. Diabetes is not only medical but also economic and social problem

Formulation and packaging

The lecture is focused on formulation and packaging of different dosage forms

Pediatric self-medication trends in Republic of North Macedonia

Aim of the study: The use of medication in children and infants represents a unique set of challenges for prescribing physician as the children are among the most vulnerable population in every society. Self-medication in children is especially important issue according to the fact that improper self-diagnosis and treatment of serious illness can lead to significant risk of drug-drug interactions as well as to an increased risk of adverse effects and potential abuse. However, self-medication provides direct and fast access to effective drugs due to their widespread availability in pharmacies. The aim of this study is to represent the most common illness for which self-medication was resorted, comparison of recommendations of guidelines from relevant world sources (WHO, FDA, MBD and others) with regulation for self-medication in Republic of Macedonia and to determine the self-medication trends in children by their parents